scholarly journals Antipsychotic Behavioral Phenotypes in the Mouse Collaborative Cross Recombinant Inbred Inter-Crosses (RIX)

2020 ◽  
Vol 10 (9) ◽  
pp. 3165-3177
Author(s):  
Paola Giusti-Rodríguez ◽  
James G Xenakis ◽  
James J Crowley ◽  
Randal J Nonneman ◽  
Daniela M DeCristo ◽  
...  
Keyword(s):  
Body Weight ◽  
Recombinant Inbred ◽  
Mixed Models ◽  
Genetic Basis ◽  
Collaborative Cross ◽  
Typical Antipsychotic ◽  
Therapeutic Approaches ◽  
Orofacial Movements ◽  
Almost All ◽  
Vacuous Chewing

Abstract Schizophrenia is an idiopathic disorder that affects approximately 1% of the human population, and presents with persistent delusions, hallucinations, and disorganized behaviors. Antipsychotics are the standard pharmacological treatment for schizophrenia, but are frequently discontinued by patients due to inefficacy and/or side effects. Chronic treatment with the typical antipsychotic haloperidol causes tardive dyskinesia (TD), which manifests as involuntary and often irreversible orofacial movements in around 30% of patients. Mice treated with haloperidol develop many of the features of TD, including jaw tremors, tongue protrusions, and vacuous chewing movements (VCMs). In this study, we used genetically diverse Collaborative Cross (CC) recombinant inbred inter-cross (RIX) mice to elucidate the genetic basis of antipsychotic-induced adverse drug reactions (ADRs). We performed a battery of behavioral tests in 840 mice from 73 RIX lines (derived from 62 CC strains) treated with haloperidol or placebo in order to monitor the development of ADRs. We used linear mixed models to test for strain and treatment effects. We observed highly significant strain effects for almost all behavioral measurements investigated (P < 0.001). Further, we observed strong strain-by-treatment interactions for most phenotypes, particularly for changes in distance traveled, vertical activity, and extrapyramidal symptoms (EPS). Estimates of overall heritability ranged from 0.21 (change in body weight) to 0.4 (VCMs and change in distance traveled) while the portion attributable to the interactions of treatment and strain ranged from 0.01 (for change in body weight) to 0.15 (for change in EPS). Interestingly, close to 30% of RIX mice exhibited VCMs, a sensitivity to haloperidol exposure, approximately similar to the rate of TD in humans chronically exposed to haloperidol. Understanding the genetic basis for the susceptibility to antipsychotic ADRs may be possible in mouse, and extrapolation to humans could lead to safer therapeutic approaches for schizophrenia.

scholarly journals Antipsychotic behavioral phenotypes in the mouse Collaborative Cross recombinant inbred inter-crosses (RIX)

2019 ◽  
Author(s):  
Paola Giusti-Rodríguez ◽  
James G. Xenakis ◽  
James J. Crowley ◽  
Randal J. Nonneman ◽  
Daniela M. DeCristo ◽  
...  
Keyword(s):  
Body Weight ◽  
Recombinant Inbred ◽  
Mixed Models ◽  
Genetic Basis ◽  
Collaborative Cross ◽  
Typical Antipsychotic ◽  
Therapeutic Approaches ◽  
Orofacial Movements ◽  
Almost All ◽  
Vacuous Chewing

ABSTRACTSchizophrenia is an idiopathic disorder that affects approximately 1% of the human population, and presents with persistent delusions, hallucinations, and disorganized behaviors. Antipsychotics are the standard pharmacological treatment for schizophrenia, but are frequently discontinued by patients due to inefficacy and/or side effects. Chronic treatment with the typical antipsychotic haloperidol causes tardive dyskinesia (TD), which manifests as involuntary and often irreversible orofacial movements in around 30% of patients. Mice treated with haloperidol develop many of the features of TD, including jaw tremors, tongue protrusions, and vacuous chewing movements (VCMs). In this study, we used genetically diverse Collaborative Cross (CC) recombinant inbred inter-cross (RIX) mice to elucidate the genetic basis of antipsychotic-induced adverse drug reactions (ADRs). We performed a battery of behavioral tests in 840 mice from 73 RIX lines (derived from 62 CC strains) treated with haloperidol or placebo in order to monitor the development of ADRs. We used linear mixed models to test for strain and treatment effects. We observed highly significant strain effects for almost all behavioral measurements investigated (p<0.001). Further, we observed strong strain-by-treatment interactions for most phenotypes, particularly for changes in distance traveled, vertical activity, and extrapyramidal symptoms (EPS). Estimates of overall heritability ranged from 0.21 (change in body weight) to 0.4 (VCMs and change in distance traveled) while the portion attributable to the interactions of treatment and strain ranged from 0.01 (for change in body weight) to 0.15 (for change in EPS). Interestingly, close to 30% of RIX mice exhibited VCMs, a sensitivity to haloperidol exposure, approximately similar to the rate of TD in humans chronically exposed to haloperidol. Understanding the genetic basis for the susceptibility to antipsychotic ADRs may be possible in mouse, and extrapolation to humans could lead to safer therapeutic approaches for schizophrenia.

scholarly journals Targeting RB1 Loss in Cancers

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3737
Author(s):  
Paing Linn ◽  
Susumu Kohno ◽  
Jindan Sheng ◽  
Nilakshi Kulathunga ◽  
Hai Yu ◽  
...  
Keyword(s):  
Cell Cycle Progression ◽  
Suppressor Gene ◽  
Therapeutic Approaches ◽  
Neighboring Gene ◽  
Genomic Aberration ◽  
Cycle Progression ◽  
Synthetic Lethal ◽  
Mitotic Kinases ◽  
Promote Cell Cycle Progression ◽  
Almost All

Retinoblastoma protein 1 (RB1) is encoded by a tumor suppressor gene that was discovered more than 30 years ago. Almost all mitogenic signals promote cell cycle progression by braking on the function of RB1 protein through mono- and subsequent hyper-phosphorylation mediated by cyclin-CDK complexes. The loss of RB1 function drives tumorigenesis in limited types of malignancies including retinoblastoma and small cell lung cancer. In a majority of human cancers, RB1 function is suppressed during tumor progression through various mechanisms. The latter gives rise to the acquisition of various phenotypes that confer malignant progression. The RB1-targeted molecules involved in such phenotypic changes are good quarries for cancer therapy. Indeed, a variety of novel therapies have been proposed to target RB1 loss. In particular, the inhibition of a number of mitotic kinases appeared to be synthetic lethal with RB1 deficiency. A recent study focusing on a neighboring gene that is often collaterally deleted together with RB1 revealed a pharmacologically targetable vulnerability in RB1-deficient cancers. Here we summarize current understanding on possible therapeutic approaches targeting functional or genomic aberration of RB1 in cancers.

scholarly journals Studying the pharmacogenomic effect of cranberry extract on reducing body weight using collaborative cross mice

2021 ◽  
Author(s):  
Fatima Amer-Sarsour ◽  
Rawan Abu Saleh ◽  
Itzhak Ofek ◽  
Fuad A. Iraqi
Keyword(s):  
Body Weight ◽  
Collaborative Cross ◽  
Diverse Backgrounds ◽  
Mouse Lines

The non-dialyzable material (NDM) of polyphenol-rich cranberry extract (CRE) powder (NDM-CRE) was studied for its effect of inducing body weight (BW) loss in 13 different mouse lines with well-defined genetically diverse backgrounds, named the collaborative cross (CC).

scholarly journals Research Regarding the Quality of Lambs Carcass Resulted from Tsigaia Purebred Compared with Hybrids of Tsigaia Ewes Crossed with Blanc du Massif Central Rams

2017 ◽  
Vol 74 (1) ◽  
pp. 7
Author(s):  
Mihai Marian BORZAN ◽  
Dana PUSTA ◽  
Liviu BOGDAN ◽  
Alexandra TABARAN ◽  
Attila MATE ◽  
...  
Keyword(s):  
Body Weight ◽  
Chemical Composition ◽  
Massif Central ◽  
Live Body Weight ◽  
Almost All ◽  
Qualitative Characteristics

Abstract: The research aims to compare some qualitative characteristics of purebred Tsigaia lambs and Tsigaia crossed with Blanc du Massif Central lambs. The criteria assessed were: chemical composition of purebred and Tsigaia crossed meat, the live body weight, the slaughtering performance, the weight of different carcass cut. For almost all criteria chosen the crossed individuals registered better results.

Breeding for Pepper yellow mosaic virus resistance and agronomic attributes in recombinant inbred lines of chili pepper (Capsicum baccatum L.) using mixed models

2021 ◽  
Vol 282 ◽  
pp. 110025
Author(s):  
Daniele Viana da Costa ◽  
Claudia Lougon de Almeida Paiva ◽  
Cíntia dos Santos Bento ◽  
Cláudia Pombo Sudré ◽  
Thâmara Figueiredo Menezes Cavalcanti ◽  
...  
Keyword(s):  
Mosaic Virus ◽  
Recombinant Inbred ◽  
Mixed Models ◽  
Virus Resistance ◽  
Recombinant Inbred Lines ◽  
Inbred Lines ◽  
Chili Pepper ◽  
Yellow Mosaic Virus ◽  
Capsicum Baccatum

scholarly journals QTL analysis of self-selected macronutrient diet intake: fat, carbohydrate, and total kilocalories

2002 ◽  
Vol 11 (3) ◽  
pp. 205-217 ◽  
Author(s):  
Brenda K. Smith Richards ◽  
Brenda N. Belton ◽  
Angela C. Poole ◽  
James J. Mancuso ◽  
Gary A. Churchill ◽  
...  
Keyword(s):  
Body Weight ◽  
Qtl Analysis ◽  
Genetic Basis ◽  
Body Weight Gain ◽  
Macronutrient Intake ◽  
Naturally Occurring ◽  
Trait Locus ◽  
Diet Intake ◽  
Insight Into ◽  
Protein Quantitative Trait Locus

The present study investigated the inheritance of dietary fat, carbohydrate, and kilocalorie intake traits in an F2 population derived from an intercross between C57BL/6J (fat-preferring) and CAST/EiJ (carbohydrate-preferring) mice. Mice were phenotyped for self-selected food intake in a paradigm which provided for 10 days a choice between two macronutrient diets containing 78/22% of energy as a composite of either fat/protein or carbohydrate/protein. Quantitative trait locus (QTL) analysis identified six significant loci for macronutrient intake: three for fat intake on chromosomes (Chrs) 8 ( Mnif1), 18 ( Mnif2), and X ( Mnif3), and three for carbohydrate intake on Chrs 17 ( Mnic1), 6 ( Mnic2), and X ( Mnic3). An absence of interactions among these QTL suggests the existence of separate mechanisms controlling the intake of fat and carbohydrate. Two significant QTL for cumulative kilocalorie intake, adjusted for baseline body weight, were found on Chrs 17 ( Kcal1) and 18 ( Kcal2). Without body weight adjustment, another significant kcal locus appeared on distal Chr 2 ( Kcal3). These macronutrient and kilocalorie QTL, with the exception of loci on Chrs 8 and X, encompassed chromosomal regions influencing body weight gain and adiposity in this F2 population. These results provide new insight into the genetic basis of naturally occurring variation in nutrient intake phenotypes.

scholarly journals Recombinant inbred lines derived from cultivars of pea for understanding the genetic basis of variation in breeders' traits

2018 ◽  
Vol 16 (5) ◽  
pp. 424-436 ◽  
Author(s):  
Carol Moreau ◽  
Maggie Knox ◽  
Lynda Turner ◽  
Tracey Rayner ◽  
Jane Thomas ◽  
...  
Keyword(s):  
Recombinant Inbred ◽  
Seed Weight ◽  
Genetic Basis ◽  
Recombinant Inbred Lines ◽  
Field Trials ◽  
Genetic Maps ◽  
Genotypic Differences ◽  
Phenotypic Data ◽  
Growing Seasons ◽  
Randomized Field Trials

AbstractIn order to gain an understanding of the genetic basis of traits of interest to breeders, the pea varieties Brutus, Enigma and Kahuna were selected, based on measures of their phenotypic and genotypic differences, for the construction of recombinant inbred populations. Reciprocal crosses were carried out for each of the three pairs, and over 200 F2 seeds from each cross advanced to F13. Bulked F7 seeds were used to generate F8–F11 bulks, which were grown in triplicated plots within randomized field trials and used to collect phenotypic data, including seed weight and yield traits, over a number of growing seasons. Genetic maps were constructed from the F6 generation to support the analysis of qualitative and quantitative traits and have led to the identification of four major genetic loci involved in seed weight determination and at least one major locus responsible for variation in yield. Three of the seed weight loci, at least one of which has not been described previously, were associated with the marrowfat seed phenotype. For some of the loci identified, candidate genes have been identified. The F13 single seed descent lines are available as a germplasm resource for the legume and pulse crop communities.

scholarly journals Pemulihan Kerusakan Jaringan Hati Mencit yang Diberi Ekstrak Butanol Buah Tua Mahkota Dewa

2018 ◽  
Vol 10 (1) ◽  
pp. 53
Author(s):  
Arif Soeksmanto
Keyword(s):  
Diabetes Mellitus ◽  
Body Weight ◽  
Medicinal Plant ◽  
Traditional Medicine ◽  
Tissue Damage ◽  
Liver Tissue ◽  
Butanol Extract ◽  
Phaleria Macrocarpa ◽  
Almost All

Mahkota dewa (Phaleria macrocarpa [Scheff.] Boerl.) is an Indonesians traditional medicinal plant used to treat various diseases, such as diabetes mellitus, hemorrhoid, impotency and cancer. Almost all parts of the plants canbe used as traditional medicine, but if directly consumed, it can cause swollen, sprue, numb at tongue, fever, even unconsciousness. This research was carried out to find out recovery of liver tissue damage of mice administered intraperitoneally with subchronic dosage of butanol extract 170 mg/kg body weight. Observation on first week showed that there is light degeneration (vacuolization) which is getting better on second week and apparentlynormal on forth week.

scholarly journals The Effect of Feeding Native Faba Bean Seeds (Vicia faba L.) to Sows and Supplemented With Enzymes to Piglets and Growing Pigs

2018 ◽  
Vol 18 (4) ◽  
pp. 1007-1027 ◽  
Author(s):  
Małgorzata Świątkiewicz ◽  
Jerzy Księżak ◽  
Ewa Hanczakowska
Keyword(s):  
Body Weight ◽  
Soybean Meal ◽  
Faba Bean ◽  
Unsaturated Fatty Acids ◽  
Body Weight Gain ◽  
Nutrient Digestibility ◽  
Growing Pigs ◽  
Control Group ◽  
Feed Mixture ◽  
Almost All

AbstractThe aim of this experiment was to examine the possibility of replacing part of soybean meal in the diets of sows, their piglets and fatteners with two varieties of high- or low-tannin faba bean seed. Twenty-four sows were allocated to 3 groups, 8 animals in each. Control group (C) received standard feed mixture containing soybean meal as the main protein source. Next groups received standard feed mixture in which part of soybean meal was replaced by high-tannin variety Bobas (group HT) or low-tannin variety Kasztelan (group LT). Faba bean was added to diets at the level of 12 and 14% for pregnant and lactating sows, 6% for piglets, and 12 and 16% for fatteners (grower and finisher, respectively). Diets for half piglets and fatteners were supplemented with the enzyme Ronozyme VP. Apparent digestibility of nutrients was evaluated in a parallel experiment, using the same feeds on 18 barrows weighing about 40 kg (grower) and 80 kg (finisher). There was almost no difference in sow reproductive rates, litter weight and body weight of piglets on the first day of life were similar. Until 35 days of age piglets receiving faba bean grew faster than control ones. Control piglets grew fastest from 35 to 84 days of age, but differences were not significant. Enzyme supplement had a positive effect on body weight only from 56 to 84 days of piglet life. Digestibility of nutrients was lower in pigs fed with faba beans, especially in the grower period. Faba bean HT had lower nutrient digestibility in both periods of fattening. Almost all carcass traits were better in control pigs than in those fed with bean variety Bobas. Meat of these pigs had also the lowest content of unsaturated fatty acids and highest atherogenic indices. In sensory evaluation this meat had also the worst smell and taste. It can be stated that faba bean seeds, in moderate amounts, can partially replace soybean meal in feed for pigs, but some lowering of body weight gain and meat quality is possible especially when high-tannin varieties are used.

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